This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Nonalcoholic steatohepatitis (NASH) occurs in 2-3% of the US population and carries a 15-20% chance of progression to cirrhosis. It is closely associated with obesity, hyperlipidemia and insulin resistance. Therapy usually includes recommendations to increase exercise and to begin weight reducing diets but these goals are variably achieved and their relative effects in conjunction with pharmacological intervention have not been well-defined. Other forms of therapy include insulin sensitizing agents but no intervention is proven or uniformly accepted. Furthermore, interpretation of pharmacological treatment results is confounded by commonly recommended life-style changes voluntarily adopted by the patient. Polyunsaturated fatty acids, especially formulations rich in omega-3 fatty, are widely accepted and endorsed in the medical community for their beneficial effects on hyperlipidemia and coronary disease risk reduction. Recent data suggests that omega 3 fatty acids ameliorate hepatic steatosis in humans and in animal models of NASH by reducing hepatic fat content. We hypothesize that a one year course of omega-3 fatty acid (3g/day) will produce improvement in NASH activity, liver fat content, and lipid profiles independent of weight loss or exercise conditioning compared to a placebo. Among commonly used supplements, omega-3 rich fish oils stand out as having won endorsement from the American Heart Association and FDA approval for a qualified health claim in coronary risk reduction. We have chosen a brand of omega-3 that exceeds purity marks set by European and Scandanavian Medicinal Standards and meets recently adopted criteria set by NCCAM. Our primary endpoint is to assess changes in a composite score of NASH-induced liver injury relative to changes in exercise tolerance and weight. Other secondary endpoints include changes in liver fat content by MRI, blood lipid profile, insulin sensitivity and markers of the metabolic syndrome after treatment. Statistical analysis will be performed to assess the impact of weight loss and changes in exercise tolerance on the primary endpoint relative to omega-3 use. This GCRC-based pilot study of 50 evaluable subjects will establish a workable platform for multicenter trials to measure the relative impact of voluntary life-style modification on potentially effective pharmacological therapy in treating NASH. An additional secondary endpoint will involve a chi square analysis to evaluate the patients requiring initiation of anti-hyperlipidemic therapy in each of the two groups.